Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
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An effective locoregional therapy is needed for adenocarcinomas of the pancreas, stomach, and gastroesophageal junction. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) may enhance the effect of radiation therapy (RT). Paclitaxel synchronizes cells at G2/M, a relatively radiosensitive phase of the cell cycle. We have shown that response to paclitaxel and concurrent RT (paclitaxel/RT) was not affected by p53 mutations in non-small cell lung cancer. This finding suggested that paclitaxel/RT was a rational treatment approach for other malignancies that frequently harbor p53 mutations, such as upper gastrointestinal malignancies. We completed a phase I study of paclitaxel/RT for locally advanced pancreatic and gastric cancer. The maximum tolerated dose of paclitaxel was 50 mg/m2/wk for 6 weeks with abdominal RT. The dose-limiting toxicities were abdominal pain within the radiation field, nausea, and anorexia. Phase II studies are now under way. Twenty-five patients with locally advanced pancreatic cancer have been entered at the phase II dose level of paclitaxel 50 mg/m2/wk with concurrent RT (total dose, 50 Gy). Thus far, the only grade 3/4 toxicities have been hypersensitivity reactions (n = 2), asymptomatic grade 4 neutropenia (n = 3), and nonneutropenic biliary sepsis (n = 1). Of the first 18 assessable patients with pancreatic cancer treated on the phase II study, six obtained a partial response, for a preliminary response rate of 33%. In the phase II study for locally advanced gastric cancer, 20 patients have been enrolled. Of the first 19 patients who have completed treatment, nine (47%) had grade 3/4 toxicities, including nausea, anorexia, esophagitis, and gastritis. Of the first 16 patients with gastric cancer, complete and partial responses have been observed in one and eight patients, respectively, for a preliminary response rate of 56%. We have also completed treatment on 24 patients with potentially resectable adenocarcinomas of the gastroesophageal junction with neoadjuvant paclitaxel 60 mg/m2 and cisplatin 25 mg/m2, weekly for 4 weeks, with concurrent RT (total dose, 40 Gy) followed by surgical resection. Ten patients (41%) had grade 3/4 toxicities, including neutropenia, nausea, and dehydration. Of 24 patients, four complete responses (17%) and 14 partial responses (58%) were observed, for an overall response rate of 75%. Severe esophagitis was uncommon, making this a well-tolerated outpatient regimen for adenocarcinomas of the distal esophagus. These findings demonstrate that paclitaxel-based chemoradiation for locally advanced upper gastrointestinal malignancies is well-tolerated with substantial activity.
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PMID:Paclitaxel and concurrent radiation therapy for locally advanced adenocarcinomas of the pancreas, stomach, and gastroesophageal junction. 1021 May 40

A recent meta-analysis and randomized studies have demonstrated that combined chemoradiotherapy is associated with a survival advantage for selected patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). We conducted a phase II study of combined chemoradiotherapy to find a more effective combination of drugs and radiation than those previously reported for such patients. Between January 1994 and November 1996, 50 previously untreated patients with locally advanced unresectable NSCLC (stage IIIA with N2 or IIIB disease) were entered in this study. Patients were required to have Eastern Cooperative Oncology Group performance status < or = 2, age < or = 75 years and adequate organ function. Treatment consisted of three cycles of cisplatin (20 mg m(-2), days 1-5) and 5-fluorouracil (5-FU) (500 mg m(-2), days 1-5) every 4 weeks, and concurrent hyperfractionated thoracic radiation (1.25 Gy twice daily, with a 6-h interfraction interval; total radiation dose, 62.5-70 Gy). Of the 50 patients entered, 37 (74%) responded to this chemoradiotherapy, including two (4%) with complete response. By a median follow-up time of 41.0 months, 35 patients had died and 15 were still alive. The median time to progression for responding patients was 14.1 months (range, 2.6-51.3+ months). The median survival time was 18.7 months, with a survival rate of 66.0% at 1 year, 46.0% at 2 years and 27.6% at 3 years. Survival outcome was strongly affected by the extent of nodal involvement (median survival time, 27.4 months for N0-2 disease (n = 37) vs 10.7 months for N3 disease (n = 13); P = 0.007). The major toxicities of treatment were leukopenia and neutropenia (> or = Grade 3, 58% and 60% respectively). Other toxicities of > or = Grade 3 included thrombocytopenia (26%), anaemia (26%), nausea/vomiting (16%) and radiation oesophagitis (6%). Treatment-related death occurred for one patient. Our findings suggest that cisplatin and 5-FU in combination with concurrent hyperfractionated thoracic radiation is effective and feasible for the treatment of locally advanced unresectable NSCLC. The short-term survival in this study appeared to be more encouraging than those of similar chemoradiation trials. A randomized trial will be needed to compare the combination of cisplatin and 5-FU with other platinum-based regimens together with concurrent hyperfractionated thoracic radiation. In addition, in future studies, inclusion criteria for N3 disease with or without supraclavicular involvement should be reconsidered to correctly evaluate the effect of combined chemoradiotherapy for locally advanced unresectable NSCLC.
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PMID:A phase II study of cisplatin and 5-fluorouracil with concurrent hyperfractionated thoracic radiation for locally advanced non-small-cell lung cancer: a preliminary report from the Okayama Lung Cancer Study Group. 1063 75

BACKGROUND: Major complications of modern bariatric operations are infrequent but can be quite disabling to the patient and pose therapeutic challenges to the surgeon. We present our experience with five patients who underwent gastrectomy for complications following gastric reduction procedures. PATIENTS AND METHODS: Between 1991 and 1995, four women and one man, average age 46.8 years (34-66), underwent total gastrectomy and Roux-en-Y end-to-side esophagojejunostomy (4), or near-total gastrectomy with esophagogastrostomy (1). The decision to perform total gastrectomy was based on the poor quality of the remaining gastric pouch and the surgeon's judgement. Preoperative diagnoses included gastric outlet obstruction secondary to anastomotic ulcer or stricture, gastroesophageal reflux with esophagitis, chronic gastrocutaneous fistula, and iatrogenic linitis secondary to gastric wrap with mesh. Preoperatively, the patients complained of intolerable nausea, vomiting, abdominal pain, and dysphagia. RESULTS: in the five patients who underwent total or near-total gastrectomy, there was no operative mortality or morbidity; however, one patient (near-total gastrectomy) has required a second operation for pyloroplasty. Although one patient was lost to follow-up 6 months after surgery, the average follow-up for the remaining four patients is 2 years. These four patients were interviewed and all report complete satisfaction with their surgery and much improvement in their symptoms. Presently, they consume an average of three meals per day (range 2-6), with each meal measuring about 2 cups in size. All report the sensation of satiety after meals. All patients receive supplemental iron, B12, and multivitamins. From a nutritional standpoint, there has not been a significant change in the levels of albumin, total protein, hematocrit, weight and BMI since total gastrectomy. CONCLUSIONS: In our experience, total gastrectomy with Roux-en-Y end-to-side esophagojejunostomy is an appropriate therapy with low morbidity and mortality in highly selected patients with complications resulting from gastric reduction procedures.
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PMID:Gastrectomy for Complications of Bariatric Procedures. 1072 78

Symptoms related to fungal esophagitis were studied in patients with alcoholic liver disease who underwent upper gastrointestinal endoscopy. Data of 517 patients were studied retrospectively (group I) and 100 alcoholic liver disease patients, that were successively admitted to hospital, were enrolled in the prospective part (group II). Out of the 41 cases with fungal esophagitis found in group I, data of 38 could be evaluated. In group II 13 of the 93 evaluable patients had fungal esophagitis; according to Kodsi's grading 10 patients had grade 1., one patient grade 2. and two patients grade 2-3. oesophagitis. There was no case with grade 4. esophagitis. The rate of symptoms among the 51 patients with fungal esophagitis was: anorexia 23 (45.0%), abdominal pain 22 (43.1%), vomiting 17 (33.3%), nausea 15 (29.4%), occult gastrointestinal bleeding 12 (23.5%), weight loss 9 (17.6%), melena 7 (13.7%), bloating 6 (11.7%), acidic regurgitation 3 (5.8%), haematemesis 2 (3.9%), thoracic pain 2 (3.9%), singultus 1 (1.9%), odynophagia 0 and dysphagia 0. In 7 patients (13.7%) none of the studied symptoms could be identified. Despite the relatively high frequency of symptom free fungal esophagitis reported in the literature, the total lack of odynophagia and dysphagia in our patient group was remarkable. In the lack of deglutition disorders the other symptoms do not raise the suspicion of esophagitis. The diagnosis in such cases can be established only by endoscopy.
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PMID:[Symptoms of fungal esophagitis in alcoholic liver disease]. 1094 8

In preclinical studies, the topoisomerase I inhibitor irinotecan (Camptosar, CPT-11) has demonstrated activity as a radiosensitizer, probably due to its ability to inhibit potentially lethal radiation damage repair. We conducted a phase I trial to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLT) of weekly irinotecan with concurrent thoracic radiation therapy for patients with unresectable stage III non-small-cell lung cancer. For this study, 13 patients received three dose escalations (from 30 to 40 to 50 mg/m2/wk). At the first dose level, one patient developed grade 5 esophagitis. Accrual was expanded to seven patients. None of the remaining six patients developed esophagitis. At the second dose level (40 mg/m2/wk), the worst toxicity, which developed in one patient, was grade 2 esophagitis. At the third dose level (50 mg/m2/wk), two of three patients developed grade 4 nausea and vomiting; grade 3 or 4 esophagitis also occurred in two patients. Of the 12 evaluable patients, seven achieved a partial response, for an overall response rate of 58%. In conclusion, nausea, vomiting, and esophagitis appear to be the principal DLTs of concurrent weekly irinotecan and thoracic radiation in the outpatient setting. The MTD of concurrent weekly irinotecan with thoracic radiation therapy appears to be 40 mg/m2 weekly for 6 weeks. To confirm the MTD of this combination, this study is still open to accrual at the second dose level (40 mg/m2) in combination with carboplatin.
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PMID:Weekly irinotecan and concurrent radiation therapy for stage III unresectable NSCLC. 1098 Dec 90

As available data on Helicobacter pylori infection in patients with diabetes are scattered and discordant, we evaluated the prevalence of H. pylori and its relationship to dyspeptic symptoms in adult patients with diabetes and subjects with dyspepsia. H. pylori infection (evaluated using the 13C urea breath test) and dyspeptic symptoms (nausea, bloating, and epigastric distress) were investigated in 71 consecutive diabetic outpatients; the presence of gross lesions, histologic gastritis, and Helicobacter was verified in the patients with a positive urea test who agreed to undergo upper gastrointestinal tract endoscopy. Seventy-one age- and gender-matched subjects with dyspepsia were used as controls. Helicobacter pylori infection was detected in 49 (69%) patients with diabetes and in 33 (46%) subject with dyspepsia (p = 0.007). Helicobacter pylori was present in 27 (77%) of 35 patients with diabetes with dyspeptic symptoms and in 22 (61%) of 36 patients without dyspeptic symptoms. Endoscopy revealed peptic ulcers in 13 of 23 patients; H. pylori infection was histologically confirmed in the gastric antrum of all patients with diabetes, and in the body of the stomach in 74%. The significantly higher prevalence of H. pylori infection in the patients with diabetes may partially explain their dyspeptic symptoms. The high prevalence of H. pylori infection, esophagitis, and peptic ulcers found in our patients with diabetes (with or without dyspepsia) suggests that this population should be considered "at risk" for H. pylori infection and suitable candidates for treatment.
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PMID:Helicobacter pylori prevalence in patients with diabetes and its relationship to dyspeptic symptoms. 1124 46

From March 1992 to October 1997, a total of 38 patients with histologically proven esophageal cancer received combination therapy of daily low-dose cisplatin (CDDP) and radiation therapy. The clinical stages (UICC 1997) were I in 3, IIA,B in 13, III in 13, and IVA in 9 patients. CDDP (5 mg/m2) was administered intravenously with 100 ml saline 30 min before each irradiation from Monday to Friday. All patients received at least 60 Gy of radiation therapy. The average number of CDDP administrations was 23, and the mean total CDDP dose was 115 mg/m2. Of the 38 patients, 14 patients completed full course of chemoradiation therapy. The overall survival rates at 1, 2, and 5 years were 51%, 19%, and 8%, respectively. The median survival period was 12 months. The objective response rate was 82% with 11 (29%) CR. Survival of the stage II-IVA patients who received daily low-dose CDDP and radiation therapy was a little better than that of historical control patients who were treated by radiation therapy alone. Most of the patients experienced nausea. Grade 3 esophagitis was observed in two (5%) patients. Grade 4 leukocytopenia and thorobocytopenia were observed in one (3%) and two (5%) of the patients, respectively. Except for leukocytopenia (18%), frequencies of toxicity of grade 3 or more were less than 10%. Although the results indicate that daily low-dose CDDP combined with radiation therapy may slightly improve the survival of esophageal cancer patients with acceptable toxicity, further efforts should be made to optimize clinical trial protocols. Escalation of daily CDDP dose should be considered to obtain a more effective radiosensitizing effect.
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PMID:A pilot study of radiation therapy combined with daily low-dose cisplatin for esophageal cancer. 1141 Jul 84

A 78-year-old male patient had esophageal carcinoma with multiple liver metastases. Chemoradiotherapy was performed. The chemotherapy consisted of protracted infusion of 5-fluorouracil (5-FU), combined with infusion of nedaplatin (NDP). Radiation of the mediastinum was administered concomitantly with chemotherapy. The patient showed a complete response (CR) of the primary lesion and a partial response (PR) of the liver metastasis for 11 months. Since liver metastasis recurred after initial treatment, chemotherapy consisting of NDP infusion combined with vindesine sulfate (VDS) infusion was performed. The patient again showed PR. Grade 3 leukocytopenia occurred during treatment, but there were no major toxicities such as thrombocytopenia, nausea, renal dysfunction or esophagitis. Survival time was one year and 7 months. In conclusion, concurrent chemoradiotherapy including NDP is effective and safe for patients with esophageal carcinoma accompanied by multiple liver metastasis. This nonsurgical approach may be an option for standard care in such cases.
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PMID:[A case of esophageal carcinoma with multiple liver metastases successfully treated with nedaplatin (NDP) and 5-fluorouracil (5-FU) combined with radiotherapy]. 1143 53

Lansoprazole is an inhibitor of gastric acid secretion and also exhibits antibacterial activity against Helicobacter pylori in vitro. Current therapy for peptic ulcer disease focuses on the eradication of H. pylori infection with maintenance therapy indicated in those patients who are not cured of H. pylori and those with ulcers resistant to healing. Lansoprazole 30 mg combined with amoxicillin 1g, clarithromycin 250 or 500mg, or metronidazole 400 mg twice daily was associated with eradication rates ranging from 71 to 94%, and ulcer healing rates were generally >80% in well designed studies. In addition, it was as effective as omeprazole- or rabeprazole-based regimens which included these antimicrobial agents. Maintenance therapy with lansoprazole 30 mg/day was significantly more effective than either placebo or ranitidine in preventing ulcer relapse. Importantly, preliminary data suggest that lansoprazole-based eradication therapy is effective in children and the elderly. In the short-term treatment of patients with gastro-oesophageal reflux disease (GORD), lansoprazole 15, 30 or 60 mg/day was significantly more effective than placebo, ranitidine 300 mg/day or cisapride 40 mg/day and similar in efficacy to pantoprazole 40 mg/day in terms of healing of oesophagitis. Lansoprazole 30 mg/day, omeprazole 20 mg/day and pantoprazole 40 mg/day all provided similar symptom relief in these patients. In patients with healed oesophagitis. 12-month maintenance therapy with lansoprazole 15 or 30 mg/day prevented recurrence and was similar to or more effective than omeprazole 10 or 20 mg/day. Available data in patients with NSAID-related disorders or acid-related dyspepsia suggest that lansoprazole is effective in these patients in terms of the prevention of NSAID-related gastrointestinal complications, ulcer healing and symptom relief. Meta-analytic data and postmarketing surveillance in >30,000 patients indicate that lansoprazole is well tolerated both as monotherapy and in combination with antimicrobial agents. After lansoprazole monotherapy commonly reported adverse events included dose-dependent diarrhoea, nausea/vomiting, headache and abdominal pain. After short-term treatment in patients with peptic ulcer, GORD, dyspepsia and gastritis the incidence of adverse events associated with lansoprazole was generally < or = 5%. Similar adverse events were seen in long-term trials, although the incidence was generally higher (< or = 10%). When lansoprazole was administered in combination with amoxicillin, clarithromycin or metronidazole adverse events included diarrhoea, headache and taste disturbance. In conclusion, lansoprazole-based triple therapy is an effective treatment option for the eradication of H. pylori infection in patients with peptic ulcer disease. Preliminary data suggest it may have an important role in the management of this infection in children and the elderly. In the short-term management of GORD, lansoprazole monotherapy offers a more effective alternative to histamine H2-receptor antagonists and initial data indicate that it is an effective short-term treatment option in children and adolescents. In adults lansoprazole maintenance therapy is also an established treatment option for the long-term management of this chronic disease. Lansoprazole has a role in the treatment and prevention of NSAID-related ulcers and the treatment of acid-related dyspepsia; however, further studies are needed to confirm its place in these indications. Lansoprazole has emerged as a useful and well tolerated treatment option in the management of acid-related disorders.
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PMID:Lansoprazole: an update of its place in the management of acid-related disorders. 1169 67

We aimed to determine if changes in the patterns of upper gastrointestinal diseases at endoscopy have occurred over the past decade. Retrospectively, 917 consecutive patients were selected based on upper endoscopy between June 1 and August 31, in 1990 (n = 217), 1994 (n = 270), and 1998 (n = 430). Demographic, clinical, endoscopic, and histological information were extracted from the medical records on a standardized case record form. Over the eight-year period, follow-up of peptic ulcer (15%, 5%, and 5%, respectively, in 1990, 1994, and 1998, df = 2, P < 0.001), bleeding (22%, 14%, and 13%, P = 0.008), and nausea/vomiting (15%, 16%, and 10%, df = 2, P = 0.003) had become less frequent, but reflux (21%, 19%, and 34%, df = 2, P < 0.001) and dyspepsia (24%, 43%, and 32%, df = 2, P < 0.001) more frequent indications for upper endoscopy. The prevalence of peptic ulcer disease decreased (22%, 15%, and 13%, df = 2, P = 0.025), but the prevalence of reflux esophagitis increased significantly (29%, 30%, and 39%, df = 2, P = 0.010). The prevalence of both the use of nonsteroidal antiinflammatory drugs (NSAIDs) (18%, 20%, and 11%, respectively, in 1990, 1994, and 1998, df = 2, P = 0.004) and H. pylori infection (39% in 1994 and 30% in 1998, df = 1, P = 0.032) decreased. Overall, NSAID use was independently associated with gastric ulcers (OR = 2.39, 95% CI 1.21-4.73, chi2 = 6.31, df = 1, P = 0.012), but not esophagitis. H. pylori infection was independently associated with duodenal ulcers (OR = 4.74, 95% CI 2.30-9.77, chi2 = 17.8, df = 1, P < 0.001), histologically chronic (OR = 166.8, 95% CI 76.1-365.4, chi2 = 313.0, df = 1, P < 0.001) and active (OR = 30.1, 95% CI 17.0-53.5, chi2 = 189.7, df = 1, P < 0.001) gastritis and lymphoid aggregates (OR = 5.49, 95% CI 3.02-9.97, chi2 = 36.3, df = 1, P < 0.001). In conclusion, the prevalence of peptic ulcer disease appears to have been decreasing, whereas reflux esophagitis has been increasing over the past decade in Western Sydney. The decreased use of NSAIDs and decline of H. pylori infection have likely both contributed to the reduction of peptic ulcer disease, but the increase in reflux esophagitis remains to be fully explained.
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PMID:Reduction of peptic ulcer disease and Helicobacter pylori infection but increase of reflux esophagitis in Western Sydney between 1990 and 1998. 1176 65


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